This protocol describes the first administration of GSK2018682 to humans. The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of GSK2018682. The study will also provide preliminary evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on total lymphocyte counts.

To investigate the safety and tolerability of single escalating oral doses of GSK2018682 [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 12 weeks ] [ Designated as safety issue: No ]

Adverse event and safety lab monitoring

To investigate effects of GSK2018682 on heart rate and blood pressure [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 12 weeks ] [ Designated as safety issue: No ]

To investigate the pharmacokinetics of single doses of GSK2018682 [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 12 weeks ] [ Designated as safety issue: No ]

Evaluate the effect of single escalating oral doses of GSK2018682 on lymphocytes (totals plus subsets) [ Time Frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 12 weeks ] [ Designated as safety issue: No ]

Reduction from baseline in lymphocyte counts obtained at different time points after dosing and at different dose levels

Part A will be used to confirm the prediction of GSK2018682 PK, assess its effects on lymphocytes, and monitor its safety profile in a single cohort (Cohort 1). Cohort 1 will consist of 4 subjects and explore 4 doses of GSK2018682 in 4 study sessions. In each session, three subjects will receive GSK2018682 and one subject will receive placebo. Thus, when the cohort completes, each subject will receive placebo and 3 doses of GSK2018682.

Drug: GSK2018682

GSK2018682

Drug: Placebo

Matched Placebo

Experimental: Part B

Part B will explore doses to refine the dose-response curve of GSK2018682 on lymphocyte suppression, as allowed by stopping criteria, in 1 or 2 cohorts of up to 15 subjects (Cohort 2 and Cohort 3). In Part B, up to six single ascending doses of GSK2018682 and one dose of placebo will be investigated in up to 8 sessions.

Drug: GSK2018682

GSK2018682

Drug: Placebo

Matched Placebo

Detailed Description:

This protocol describes the first administration of GSK2018682 to humans. The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of GSK2018682. The study will also provide preliminary evidence of the potential therapeutic dose-range by measuring the inhibitory effect of GSK2018682 on total lymphocyte counts.

Eligibility

Ages Eligible for Study:

18 Years to 55 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters significantly outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with lymphocyte counts outside the normal range should always be excluded from enrollment

Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

A positive pre-study drug/alcohol screen.

A positive test for HIV antibody.

History of regular alcohol consumption

Subjects with a history of, or examination suspicious for, skin cancer(s) including melanoma, basal cell or squamous cell carcinoma.

Systolic blood pressure less than 95 mmHg or greater than 140 mmHg, or diastolic blood pressure less than or equal to 50 mmHg or greater than or equal to 95 mmHg.

Symptomatic reduction in blood pressure after orthostatic challenge.

Subjects with resting heart rate less than 45 beats per minute or greater than 90 beats per minute

Other criteria may apply as defined by the clinical protocol.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01387217